Peptide and protein biomarkers for type 1 diabetes mellitus
A method for identifying persons with increased risk of developing type 1 diabetes mellitus, or having type I diabetes mellitus, utilizing selected biomarkers described herein either alone or in combination. The present disclosure allows for broad based, reliable, screening of large population bases. Also provided are arrays and kits that can be used to perform such methods.
1. An array, comprising:
a solid support; and
antibodies covalently attached to the solid support, wherein the antibodies are specific for any combination of at least two, at least three, at least four, or at least five, type I diabetes mellitus (T1DM)-related protein sequences listed in Tables 6a or 6b.
2. The array of claim 1 , wherein the antibodies covalently attached to the solid support comprise antibodies specific for each of:
the peptide sequences shown in SEQ ID NOS: 1-52;
the peptide sequences shown in SEQ ID NOS: 23, 24, 25, 37, 38, 39, 40, 41, 47, 48, 49, 50, 51, and 52;
the peptide sequences shown in SEQ ID NOS: 37, 38, 39, 41, 47, 48, 49, and 50;
the 24 proteins listed in Table 6a;
the five proteins listed in Table 6b;
platelet basic protein (PPBP) or its various cleavage forms;
plasma protease C1 inhibitor (SERPING1); or
PGLYRP2, PPBP and SERPING1.
3. The array of claim 1 , wherein the antibodies covalently attached to the solid support comprise antibodies specific for at least eight peptides selected from the group consisting of the amino acid sequence shown in SEQ ID NO: 23, 24, 25, 37, 38, 39, 40, 41, 47, 48, 49, 50, 51, and 52, wherein at least one of the eight peptides consists of the amino acid sequence shown in SEQ ID NO: 25, 38, 39, 40, or 50.
4. The array of claim 1 , wherein the antibodies covalently attached to the solid support comprise antibodies specific for each of the amino acid sequences shown in SEQ ID NO: 23, 24, 25, 37, 38, 39, 40, 41, 47, 48, 49, 50, 51, and 52.
5. The array of claim 1 , wherein the antibodies covalently attached to the solid support comprise antibodies specific for at least eight peptides consisting of the amino acid sequence shown in SEQ ID NO: 37, 38, 39, 41, 47, 48, 49, and 50.
6. The array of claim 1 , wherein the antibodies covalently attached to the solid support comprise antibodies specific for at least one of the amino acid sequences shown in SEQ ID NO: 25, 38, 39, 40, or 50, in addition to an antibody specific for:
NIQSLEVIGK (SEQ ID NO: 41);
LLDSLPSDTR (SEQ ID NO: 48);
NIQSLEVIGK (SEQ ID NO: 41) and LLDSLPSDTR (SEQ ID NO: 48);
FQPTLLTLPR (SEQ ID NO: 47);
LVLLNAIYLSAK (SEQ ID NO: 49);
TNLESILSYPK (SEQ ID NO: 50);
FQPTLLTLPR (SEQ ID NO: 47), LLDSLPSDTR (SEQ ID NO: 48), LVLLNAIYLSAK (SEQ ID NO: 49), and TNLESILSYPK (SEQ ID NO: 50);
NIQSLEVIGK (SEQ ID NO: 41), FQPTLLTLPR (SEQ ID NO: 47), LLDSLPSDTR (SEQ ID NO: 48), LVLLNAIYLSAK (SEQ ID NO: 49), and TNLESILSYPK (SEQ ID NO: 50), or
combinations thereof.
7. The array of claim 1 , wherein the antibodies covalently attached to the solid support comprise antibodies specific for at least one of the amino acid sequences shown in SEQ ID NO: 25, 38, 39, 40, or 50, wherein at least one of the peptides is SEQ ID NO: 38 or 39.
8. The array of claim 1 , wherein the solid support is a lateral flow device.
9. The array of claim 1 , wherein the solid support comprises a multi-well plate.
10. The array of claim 1 , wherein the solid support comprises a bead.
11. A kit for diagnosing type I diabetes mellitus, comprising:
the array of claim 1 ; and
a buffer solution in separate packaging.
12. A kit for diagnosing type I diabetes mellitus, comprising:
the array of claim 1 ; and
a detection reagent in separate packaging.
13. A kit for diagnosing type I diabetes mellitus, comprising:
the array of claim 1 ; and
a conjugating solution in separate packaging.